The ET-CTN is poised to provide break-through advances in our management of cancer. For the ET-CTN to realize this opportunity, it needs to effectively navigate many scientific and operational issues in early phase drug development. To address these challenges, we propose a new strategic partnership in early oncology drug development across the Duke Cancer Institute, the Lineberger Comprehensive Cancer Center at UNC, and the Siteman Cancer Center at Washington University. The Duke-UNC-Wash U Partnership creates an ET-CTN site composed of three of the nation's NCI-designated Comprehensive Cancer Centers and leverages their combined clinical and scientific expertise to advance drug development in cancer. This Partnership provides world class breadth and depth, both clinically and scientifically, to meet the goals of the ET-CTN. Combined, this partnership manages over 18,000 new cancer cases per year; in 2012, the three centers enrolled more than 3,200 new patients onto early phase clinical trials similar to the ones envisioned by the ET-CTN. Our site has both the clinical expertise and the clinical volumes needed for the study of novel agents targeting niche populations, and our site will connect the ET-CTN to our tremendous basic and translational cancer research communities from which new drugs and therapeutic approaches are likely to emerge. We also have particular expertise in the management of multi-center studies and the analysis of biomarkers on these studies, experience directly relevant to the ET-CTN. We also bring world class expertise in molecular genomic and proteomic profiling and biomarker development. The Duke-UNC-Wash U Partnership will help achieve ET-CTN goals through the following specific steps; (1) engaging world class disease and translational teams that are collaborative and team-science oriented; (2) developing innovative strategies and approaches for development of novel anti-cancer agents and combination regimens and participating in ET-CTN project teams to generate drug development plans for novel approaches; (3) efficiently developing high-quality formal proposals and protocols in response to requests from the NCI's Cancer Therapy Evaluation Program (CTEP); (4) effectively managing trials and accruing rapidly to all ET-CTN trials; and (5) translating information gained from the trials and correlative studies, both bench-to-bedside and bedside-to-bench; and (6) mentoring new investigators and fellows in oncology drug development. To match our clinical and scientific strengths, particular emphasis will be placed upon novel therapies and combinations that target specific genetic alterations, altered signaling pathways, host immune responses, and angiogenesis and other stromal responses.